Hydrogel-coated microneedle biosensor for selective and low-potential glucose detection in skin-mimicking interstitial fluid phantoms

The development of minimally invasive biosensors for continuous glucose monitoring has attracted considerable attention to improve patient compliance and comfort. In this study, a hydrogel-coated microneedle (MN) biosensor was designed and fabricated for the selective and low-potential electrochemical detection of glucose in skin-mimicking interstitial fluid (ISF) phantoms. Stainless steel MNs were modified with a glucose oxidase (GOx)-chitosan composite and further encapsulated within an alginate-polyvinyl alcohol (Alg-PVA) hydrogel matrix to enhance biocompatibility and analyte diffusion. The GOx immobilization method, the hydrogel composition, and the drying process were optimized. Cyclic voltammetry (CV) confirmed successful fabrication and efficient electron transfer. The biosensor exhibited a wide linear detection range of 1.0–50.0 mM with a limit of detection (LOD) of 0.11 mM in phosphate-buffered saline (PBS) and a linear range of 1.0–40.0 mM with an LOD of 0.20 mM in artificial ISF. The optimized low operating potential (−0.2 V) significantly minimized interference from common electroactive species such as ascorbic acid (AA), uric acid (UA), and acetaminophen (AP). Stability assessments demonstrated excellent repeatability (RSD <4 %) and reliable performance over a 14-day storage period. Furthermore, glucose measurements performed in skin-mimicking gel-based PBS and artificial ISF phantoms exhibited a linear response range of 1.0–25 mM and an LOD of 0.11 mM and linear response range of 1.0–40.0 mM and an LOD of 0.46 mM, respectively. These results demonstrate the practical applicability and reliability of the hydrogel-coated microneedle biosensor for accurate, painless, and real-time glucose monitoring under physiologically relevant conditions, highlighting its potential for wearable healthcare applications.